Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus
Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus
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DOI：
10.1165/rcmb.2005-0287oc
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发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Garofalo, RP
中科院分区：
文献类型：
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作者：
Guerrero-Plata, A;Casola, A;Garofalo, RP
树突状细胞（DC）在塑造呼吸道抗病毒免疫反应中发挥着关键作用。人类偏肺病毒 (hMPV) 是最近发现的一种病原体，与其更为人所知的近亲呼吸道合胞病毒 (RSV) 一样，越来越多地被认为是婴儿和老年人呼吸道疾病的主要原因。在本研究中，我们检测了人类 DC 与 RSV 相比对 hMPV 的敏感性以及细胞反应。单核细胞衍生的 DC (moDC) 对两种病毒都敏感，但只有 RSV 能够诱导有效感染并释放病毒后代。尽管病毒感染导致moDC表型成熟，如细胞表面标志物和抗原呈递分子（MHC I和II、CD80、CD83、CD86、CD38）的上调所示，但RSV感染的moDC刺激CD4(+) T细胞增殖的能力严重受损。与 hMPV 相比，RSV 是 moDC 和浆细胞样树突状细胞 (pDC) 中更有效的炎症和免疫调节细胞因子诱导剂，包括 TNF-α、IL-6、IL-1 β、IL-10 和 IL-12p70。另一方面，hMPV（而非 RSV）能够触发 moDC 产生 IFN-α，而两种病毒均强烈诱导 pDC 产生 IFN-α。最后，两种病毒均显着抑制分别用合成 dsRNA 和 CpG-ODN 刺激的 moDC 或 pDC 产生 IFN-α。这些发现提供了新的证据，表明 RSV 和 hMPV 差异性地激活人类 DC，并可能使用不同的机制来干扰宿主先天性和适应性免疫反应。
Dendritic cells (DCs) play a pivotal role in shaping antiviral immune responses in the respiratory tract. Human metapneumovirus (hMPV) is a recently identified pathogen and like its better known relative, respiratory syncytial virus (RSV), has been increasingly recognized as a major cause of respiratory morbidity in infants and in elderly persons. In the present study, we examined susceptibility as well as cellular responses of human DCs to hMPV compared with RSV. Monocyte-derived DCs (moDCs) were susceptible to infection by both viruses, but only RSV was able to induce a productive infection with release of viral progeny. Despite the fact that viral infection resulted in phenotypic maturation of moDCs, as shown by the upregulation of cell surface markers and antigen-presenting molecules (MHC I and II, CD80, CD83, CD86, CD38), RSV-infected moDCs showed a severely impaired capacity to stimulate CD4(+) T cell proliferation. Compared with hMPV, RSV was a more potent inducer of inflammatory and immunomodulatory cytokines, including TNF-alpha, IL-6, IL-1 beta, IL-10, and IL-12p70 in both moDCs and plasmacytoid dendritic cells (pDCs). On the other hand, hMPV, but not RSV, was able to trigger production of IFN-alpha by moDCs, while both viruses strongly induced IFN-a in pDCs. Finally, both viruses strikingly suppressed IFN-alpha production by moDCs or pDCs stimulated with synthetic dsRNA and CpG-ODN, respectively. The findings provide novel evidence that RSV and hMPV differentially activate human DCs and may use distinct mechanisms to interfere with the host innate and adaptive immune responses.